Cardioprotection with angiotensin converting enzyme inhibitor and angiotensin II type I receptor antagonist is not abolished by nitric oxide synthaseinhibitor in ischemia-reperfused rabbit hearts

Although angiotensin converting enzyme (ACE) inhibitor and/or angiotensin I I type 1 (AT1) receptor antagonist can protect the myocardium against ische mia-reperfusion injury, the mechanisms of the effect have not yet been char acterized at the cellular level. We here examined the effect of the combina tion of an ACE inhibitor, temocaprilat, an AT1 receptor antagonist, CV-1197 4 and/or a nitric oxide synthase inhibitor, L-NAME, on the myocardial metab olism and contraction during ischemia and reperfusion by using phosphorus 3 1-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts. After normothermic 20 min global ischemia, postischemic reperfusion of 30 min was carried out. Twenty-one hearts were divided into three experimental groups consisting of 7 hearts each: a Tem+CV group perfused with a combination of temocaprilat and CV-11974; a Tem+CV+L-NAME group perfused with a combinati on of temocaprilat and CV-11974 plus L-NAME, and a control group. During is chemia, both the Tem+CV group and Tem+CV+L-NAME group showed a significant inhibition of the decrease in adenosine triphosphate (ATP) compared with th e control group (p<0.01); the increase in ATP was 50+/-3%, 42+/-4%, and 19/-4% in the Tem+CV group, Tem+CV+L-NAME group, and control group, respectiv ely. Both experimental groups also showed a significant inhibition of the i ncrease in left ventricular end-diastolic pressure (LVEDP) compared with th e control group (p<0.01). After postischemic reperfusion, the Tem+CV group and Tem+CV+L-NAME group again showed a significant improvement of ATP as co mpared with the control group (p<0.01); the increase in ATP was 73+/-3%, 64 +/-3%, and 47+/-4% in the Tem+CV group, Tem+CV+L-NAME group, and control gr oup, respectively, and a significant decrease of LVEDP as compared with the control group (p<0.01). There were no differences in ATP, or LVEDP during ischemia and reperfusion between the Tem+CV group and Tem+CV+L-NAME group. In conclusion, the combination of temocaprilat and CV-11974 showed signific ant potential for improving myocardial energy metabolism and relaxation dur ing both myocardial ischemia and reperfusion. This beneficial effect was no t dependent on NO synthase.